S243: ANTIBODY AND T-CELL RESPONSE SIX MONTHS AFTER INITIATION OF BNT162B2 VACCINATION IN PATIENTS WITH MULTIPLE MYELOMA OR CHRONIC LYMPHATIC B-CELL LEUKEMIA COMPARED TO HEALTHY CONTROLS
Authors: L. D. Heftdal, L. Pérez-Alós, S. R. Ham, J. R. Madsen, K. Fogh, C. C. Kronborg, A. P. Vallentin, R. B. Hasselbalch, S. R. Ostrowski, R. Frikke-Schmidt, E. Sørensen, L. Hilsted, H. Bundgaard, K. Iversen, P. Garred, S. D. Nielsen, K. Grønbæk
Journal: HemaSphere (2022)

Background: The ongoing COVID-19 pandemic has resulted in more than 419 million cases and more than 5.9 million deaths. Previous studies have indicated inferior responses to SARS-CoV-2 vaccination across different hematological diseases. Through this prospective cohort study, we examined the development and durability of anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients with either multiple myeloma (MM) or Chronic Lymphatic B-cell Leukemia (B-CLL) six months after vaccination and compared to immunocompetent controls. Aims: We aimed to investigate the durability of immune responses to COVID-19 vaccination in patients with MM or B-CLL compared to healthy controls, and to identify risk factors for humoral non-response, including type of diagnosis. Methods: We measured anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients (MM: n=78, B-CLL: n=101) and 179 age and sex matched healthy controls up to six months after first vaccination. Anti-RBD IgG levels and neutralizing capacity of antibodies were measured at first and second dose of BNT162b2 and two and six months after first dose. Humoral response was defined as anti-RBD IgG > 225 AU/mL with a neutralizing index ≥ 25%. Humoral non-response was defined as the absence of a humoral response. T-cell responses were assessed six months after the first dose using an ELISA-based interferon-gamma release assay. A positive T-cell response was defined as IFN-ɣ release > 200 mIU/mL. Data on diagnoses were obtained through medical records, and data on vaccination status were obtained from the Danish Vaccination Register. Results: In patients with MM or B-CLL, the geometric mean concentration (GMC) of anti-RBD IgG increased from baseline 1.49 AU/mL (95% CI: 1.21-1.84) to three weeks after the first vaccine dose 15.10 AU/mL (95% CI: 9.39-24.29) and after receiving the second dose 1179.60 AU/mL (95% CI: 727.78-1919.85). From two to six months after first vaccine there was a significant decline in the GMC of anti-RBD IgG to 252.75 AU/mL (95% CI: 159.17-403.43). The mean neutralizing capacity in patients with MM or B-CLL was lower than in controls at all time points after the first vaccine dose. Six months after first vaccine dose, 79 of 179 (44.1%) patients with MM or B-CLL had a positive humoral response, while this was the case for 170 of 179 controls (95.0%), p<0.001. Having MM or B-CLL was significantly associated with risk of humoral non-response. This was most pronounced in B-CLL patients who had an age and sex adjusted risk ratio (RR) of 12.25 (95% CI: 6.42-23.38, p< 0.001) of humoral non-response compared to healthy controls. For MM patients the RR was 4.65 (95% CI: 2.21-9.80, p< 0.001). T-cell response was assessed in a subset of 48 patients with MM (n=28) or B-CLL (n=20) and 26 controls, six months after first vaccine dose. A total of 21 (43.8%) patients with MM (12/28) or B-CLL (9/20) and 14 (53.8%) controls had a positive T-cell response (p =0.56). Seven of 20 (35.0%) patients with MM or B-CLL who did not develop a humoral response, developed a T-cell response (MM: 3/8, B-CLL: 4/12), while 14 of 28 (50.0%) patients with MM or B-CLL who developed a humoral response developed a T-cell response (p =0.46, MM: 9/11, B-CLL: 5/8). In healthy controls 14 of 25 (56.0%) people who developed a humoral response also developed a T-cell response. Summary/Conclusion: Humoral response to BNT162b2 was impaired in patients with MM or B-CLL compared to healthy controls. Both patients with MM and B-CLL were at higher risk of humoral non-response compared to healthy controls.